1. Field of the Invention
The inventions relate in general to methods and devices for performing fluid separation. In particular, the inventions relate to methods and devices by which fluid, such as blood or other biological fluids, can be separated into constituents using a centrifuge, and those constituents can be maintained in separate strata after centrifugation.
2. Background of the Invention
Many medical diagnostic procedures require a sample of biological fluids, such as blood, to be taken from a patient. Often, blood is stored in a container immediately upon removal from the patient, and the blood can be further processed while in that container. Although blood is referred to herein as an example of fluid for use with the disclosed invention, many other types of fluids could be used as well.
Blood is often stored in a fluid-tight, sterile test tube. Blood can be processed while in a test tube in many ways, such as by adding chemical reagents to the tube, or by spinning or shaking the tube, or by performing a combination of chemical and physical operations. One common approach is to rapidly spin a test tube containing blood in order to cause various components of the blood to separate into layers or strata with different densities. Such a separation process can be accomplished using a centrifuge. Blood separation can be desirable because most medical blood tests are performed on a non-cellular blood fraction. Thus, it can be helpful to concentrate the non-cellular blood fraction in one portion of a test tube and concentrate other constituents, such as a cellular fraction which can include red blood cells and/or the “buffy coat,” in a different portion of the test tube. This separation can prevent the components from chemically interfering with each other and can also arrest biochemical processes that may otherwise continue ex vivo in the mixed blood.
For many tests, the blood must be separated into components within a short time period after being drawn from the patient. Thus, even if blood tests are most efficiently done in a dedicated facility that is off site from the healthcare provider where the sample is drawn, it is often advantageous for the health care provider who draws the sample to separate the blood into constituents before shipping the blood to the laboratory, for example. However, after blood has been separated into constituents, if the blood is removed from a centrifuge, the constituent layers can begin to mix together again, thus losing the stratification accomplished through centrifugation. This loss of stratification has disadvantages, especially if the tests cannot be performed immediately after centrifugation. Stratification is especially difficult to maintain if the blood samples are jostled during the shipping process.
One approach to maintaining stratification is through the use of a wax or gel separator. Commonly, gel separators are placed inside test tubes before a blood sample is drawn. The gel generally adheres in a ring to the sides of the test tube, with a passage through the center of the gel, or at the bottom of the test tube, allowing blood to fill the remainder of the test tube. In this initial state, the gel does not block or seal off any portion of the test tube other than the portions filled by the gel itself. However, under the appropriate conditions, the gel can be activated and come away from the sides of the test tube. The appropriate conditions for gel activation are typically when the centrifuge reaches a certain rotation speed, or when a particular chemistry is achieved within the tube. Gel separators can be chosen to have a density that will position the gel strata between blood constituents during centrifugation, and the gel material can be chosen to have a different density from that of other strata. When the gel is activated, it is free to flow to the appropriate position within the test tube to form a layer that corresponds to its relative density with respect to the other fluid components. Thus, the gel can form one of the strata within the processed fluid after centrifugation, coming together into a continuous layer that effectively separates some blood constituent strata from others, thereby preserving the separation originally accomplished through centrifugation.
Although gel separators are widely used to preserve blood separation, there are many drawbacks to using gel separators to maintain blood stratification in medical samples. For example, reagents or chemicals are commonly added to blood samples to prepare the sample for a test or to react with the blood constituents. Often, the additives are injected into the empty container before the container is filled with the blood sample. However, the additives are generally not used in containers with gel separators because of the risk of chemical interaction between the gel material and the additives. Indeed, the gel material may not function properly in the presence of the extra chemicals. Similarly, the gel separator material can react with and/or modify the chemicals or reagents, inhibiting the proper functioning of the biological tests to be performed on the blood sample. Thus, the tests that are performed without the benefit of a gel separator must often be performed without the benefit and efficiencies of a laboratory because the blood must generally be centrifuged and tested within a short time after being drawn.
Another drawback of gel separators is the expense of supplying them and other supporting chemicals. For example, many different suppliers may have different formulas for their gel separators. When a testing laboratory desires to change from one gel or test tube supplier to another, the laboratory's protocols, centrifuge settings, temperatures, etc. may not be optimized for the gels supplied by the new supplier. Thus, many suppliers also agree to provide “buffer adjustors,” or chemical additives for use by the laboratory that, when added to the gel materials or samples, will adjust the chemical properties of the supplied gel so that the new material behaves similarly to those supplied by the previous supplier. The adjustors can be chemicals that are added before processing to help provide the proper chemical balance needed for the gel material to respond properly to centrifugation, for example. Thus, a laboratory can keep the same equipment, temperatures, and/or other settings if the proper buffer adjustors are provided. Buffer adjustors can adjust many parameters, including: the temperature at which the gel material becomes active; the viscosity and/or change in viscosity of the gel over a range of temperatures and/or centrifuge speeds; and the density or mass-to-weight ratio of the gel. Buffer adjustors may be required to neutralize the chemical effects of the gel separators themselves so the gel does not interact improperly with the fluid (e.g., blood) to be tested. However, the need to provide and use such buffer adjustors can lead to increased costs and inefficiencies for suppliers of gel separators and for testing laboratories.
Another drawback of gel separators is that the gel density is often designed to place the gel stratum at a certain layer within the blood constituents only after the blood has undergone some degree of coagulation. Upon removal from the patient, the fluid can often undergo biological changes. In particular, red blood cells can begin a clotting or coagulating process upon removal from the body that causes the cells to become denser. Many gels are in fact denser than the red blood cells before coagulation, but after the erythrocytes have undergone ten minutes of coagulation, they can surpass the gels in density. Thus, in many cases, stratification will not work properly until after a delay (e.g., until 10 minutes after blood withdrawal). However, the separation may not be optimal if too much time has elapsed either, due to the risk of the blood cells lysing and thereby releasing their contents and making the sample unusable. Consequently, busy health care workers are given a series of additional time constraints within which to perform their duties for processing of blood samples.
A further drawback to gel separators is the expense required to manufacture them. Gel separators can cause inefficiencies in manufacturing because the gel material is a chemical component that is best inserted after other tube components are brought together and finished. Furthermore, the manufacturing process can involve a process by which the air within the tube is substantially vacuumed out and the tube is closed. Manufacturing approaches can thus require a separate, expensive, and time-consuming process that diverts the test tubes into a chemical processing portion with separate controls and standards.
Thus, a need exists for methods and devices for facilitating and maintaining fluid separation that address the foregoing drawbacks and shortcomings.